Major Depressive Disorder is one of the most common complications of pregnancy, with 7.5% of women having an incident episode during the 9 months of pregnancy and 6.5% with an episode in the first 3 months postpartum. The overarching goal in this OPRC submission is to develop guidelines to optimize the safety and effectiveness of SSRI antidepressant treatment in pregnant women. This application responds to several priorities from the OPRC RFA, including establishing interdisciplinary approaches to understand the pharmacokinetics and/or pharmacodynamics of medications. The PI team includes Katherine L. Wisner, MD MS (psychiatry); Catherine Stika, MD (obstetrics), and Alfred George, MD (pharmacogenomics). The Administrative Core will provide the infrastructure for collaboration with the OPRC network and within the 3 main OPTI-MOM projects identified below, which have strong complementarity: 1. The Clinical Research Project. -Assess the safety and toxicity of drugs during pregnancy and the postpartum periods. The progressive changes in plasma SSRI and metabolite concentrations across pregnancy and after birth will be determined in an observational study. Serial evaluations of depressive and anxiety symptoms and side effects will be obtained to evaluate their association with plasma concentrations at monthly intervals during pregnancy and twice post-birth. To assess the subjects' metabolic phenotypes, a probe drug cocktail will be given to evaluate the activities of CYP2D6, 2C19, 2C9 and 3A4 during the third trimester (when activity change is maximal) compared to the non-pregnant state after birth. 2. The Basic/Translational Research Project -Perform clinical research to understand mechanisms of pregnancy related changes in drug response and disposition and --Identify biomarkers for safe and effective treatment of pregnancy-related conditions. In this study we will investigate the impact of genomic variability on inter-individual differences in SSRI dosing, plasma concentrations and pharmacodynamics during pregnancy, with a focus on genes involved in the metabolism of SSRIs, drug transporters responsible for SSRI access to the central nervous system, and genes encoding SSRI targets involved in therapeutic efficacy. 3. The Pilot Project -Assess the safety and toxicity of the drugs during pregnancy, postpartum, and in postnatal periods of development. This project will determine the maternal-fetal plasma concentrations and pharmacogenetic characteristics associated with neonatal SSRI abstinence syndrome. Maternal and fetal CYP and P-glycoprotein genotypes will be assessed for their relationship to SSRI drug concentrations and neonatal abstinence syndrome.